My research interests are diverse but focused. I have a firm interest in bone tumors and a soft spot for soft tissue sarcomas, including understanding the underlying pathophysiology and translational work in the clinical pathology lab setting. I joined the 2019-2021 cohort within the Children’s Oncology Group Young Investigator Program with a focus in the bone tumor group. I also am interested in exploring cell signaling and cell-to-cell communication through conventional molecular and proteomic analysis with fellow investigators. My second area of research interest is in gastrointestinal pathology, particularly eosinophilic esophagitis (EoE). Through these EoE projects, I enjoyed expanding my experience in immunology which builds on an interest during my fellowship at Lurie Children’s Hospital of Chicago, which explored transplant immunology and the effect on the gastrointestinal tract. I also enjoy expanding my experience in the area of transplant immunology. My last primary area of interest is in developmental pathology, which often stems from identifying common pathologic findings in the interesting cases I encounter at BC Children’s and Women’s Hospital. I have an interest in leadership and administration, which blossomed during my time as Cohort 2 in the BC Patient Safety and Quality Council’s Clinician Quality Academy.
Publications
Immunohistochemical study of histone protein 3 modification in pediatric osteosarcoma identifies reduced H3K27me3 as a marker of poor treatment response PLOS ONE Sebastian Kondratowski and Danielle Cohen and Rebecca J. Deyell and Ash Sandhu and Jonathan W. Bush DOI: 10.1371/journal.pone.0309471 11/2024
ASAP-Automated Sonication-Free Acid-Assisted Proteomes-from Cells and FFPE Tissues. Analytical chemistry Barnabas GD and Verena Goebeler and Tsui J and Bush JW and Philipp F. Lange DOI: 10.1021/acs.analchem.2c04264 PubMed: 36724070 02/2023
Multi-omic profiling of the leukemic microenvironment shows bone marrow interstitial fluid is distinct from peripheral blood plasma. Experimental hematology & oncology Nierves L and Guo J and Chen S and Tsui J and Uzozie AC and Bush JW and Huan T and Lange PF DOI: 10.1186/s40164-022-00310-0 PubMed: 36109804 09/2022
Application of the Eosinophilic Esophagitis Histology Scoring System Grade Scores in Patients at British Columbia Children's Hospital. Fetal and pediatric pathology Cruz J and Michael Irvine and Vishal Avinashi and Edmond Chan and Vallance BA and Lianne Soller and Bruce Vallance DOI: 10.1080/15513815.2022.2028950 PubMed: 35094661 01/2022
Quantifying Proximal Collecting Tubule Deficiency in Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Fetopathy Pediatric and Developmental Pathology Jessica Saunders and Allison Marie Callejas Salgado and Joseph Y Ting and Cherry Mammen and Jefferson Terry and Jonathan W Bush DOI: 10.1177/10935266211018922 09/2021
SMARCA4 -deficient rhabdoid tumours show intermediate molecular features between SMARCB1 -deficient rhabdoid tumours and small cell carcinomas of the ovary, hypercalcaemic type The Journal of Pathology Mamy Andrianteranagna and Joanna Cyrta and Julien Masliah-Planchon and Karolina Nemes and Alice Corsia and Amaury Leruste and Dörthe Holdhof and Uwe Kordes and Daniel Orbach and Nadège Corradini and Natacha Entz-Werle and Gaëlle Pierron and Marie-Pierre Castex and Anne Brouchet and Noëlle Weingertner and Dominique Ranchère and Paul Fréneaux and Olivier Delattre and Jonathan Bush and Alexandra Leary and Michael C. Frühwald and Ulrich Schüller and Nicolas Servant and Franck Bourdeaut DOI: 10.1002/path.5705 05/2021
Atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutation are molecularly distinct from SMARCB1-deficient cases Acta Neuropathologica Dörthe Holdhof and Pascal D. Johann and Michael Spohn and Michael Bockmayr and Sepehr Safaei and Piyush Joshi and Julien Masliah-Planchon and Ben Ho and Mamy Andrianteranagna and Franck Bourdeaut and Annie Huang and Marcel Kool and Santhosh A. Upadhyaya and Anne E. Bendel and Daniela Indenbirken and William D. Foulkes and Jonathan W. Bush and David Creytens and Uwe Kordes and Michael C. Frühwald and Martin Hasselblatt and Ulrich Schüller DOI: 10.1007/s00401-020-02250-7 2020
Poor Correlation of Oral Swabs with Esophageal Eosinophil Counts. Dysphagia Avinashi V and Chan JM and Bush JW and Vallance BA and Yang H and Portales-Casamar E and Soller L and Mill C and Chan ES DOI: 10.1007/s00455-019-10082-1 PubMed: 31773332 11/2019
Novel Exonic Deletions in TTC7A in a Newborn with Multiple Intestinal Atresia and Combined Immunodeficiency Journal of Clinical Immunology Jessica R. Saunders and Anna Lehman and Stuart E. Turvey and Jie Pan and Evica Rajcan-Separovic and Aleixo M. Muise and Jonathan W. Bush DOI: 10.1007/s10875-019-00669-6 08/2019
Systematic testing and specificity mapping of alloantigen-specific chimeric antigen receptors in regulatory T cells. JCI insight Nicholas Dawson and Caroline Lamarche and Hoeppli RE and Bergqvist P and Fung VC and McIver E and Huang Q and Gillies J and Speck M and Orban PC and Jonathan Bush and Mojibian M and Megan K. Levings DOI: 10.1172/jci.insight.123672 PubMed: 30753169 03/2019
Pediatric Pathology Fellowship Recruitment—Report of a Survey Conducted by the Fellowship Committee of the Society for Pediatric Pathology Pediatric and Developmental Pathology Singh, V. and Eldin, K. and Timmons, C. and Bush, J. and Rabah, R. DOI: 10.1177/1093526617722905 2018
Eosinophilic density in graft biopsies positive for rejection and blood eosinophil count can predict development of post-transplant digestive tract eosinophilia Pediatric Transplantation Bush, J.W. and Mohammad, S. and Melin-Aldana, H. and Kagalwalla, A.F. and Arva, N.C. DOI: 10.1111/petr.12693 2016
Treatment of neuroblastoma in congenital central hypoventilation syndrome with a PHOX2B polyalanine repeat expansion mutation: New twist on a neurocristopathy syndrome Pediatric Blood and Cancer Armstrong, A.E. and Weese-Mayer, D.E. and Mian, A. and Maris, J.M. and Batra, V. and Gosiengfiao, Y. and Reichek, J. and Madonna, M.B. and Bush, J.W. and Shore, R.M. and Walterhouse, D.O. DOI: 10.1002/pbc.25572 2015
Combined robotic and open approach to excision of accessory bladder and urethral triplication Journal of Pediatric Urology Bowen, D.K. and Glaser, A.P. and Bush, J.W. and Cheng, E.Y. and Gong, E.M. DOI: 10.1016/j.jpurol.2014.11.009 2015
Deconstructing the diagnosis of hemophagocytic lymphohistiocytosis using illustrative cases Journal of Hematopathology Weinstein, J.L. and Badawy, S.M. and Bush, J.W. and Schafernak, K.T. DOI: 10.1007/s12308-015-0254-3 2015
Intracranial atypical teratoid/rhabdoid tumor presenting as an axillary mass: A case report and review of literature Pediatric and Developmental Pathology Bush, J.W. and Hancock, B.J. and Israels, S.J. and Ellison, D.W. and Stefanovici, C. and Krawitz, S. DOI: 10.2350/14-01-1427-CR.1 2014
Sarcoma including the role of SWI/SNF proteins Rhabdoid tumors are a group of primitive cancers that are often highly aggressive and are generally defined by a mutation in the SWI/SNF pathway, including the genes SMARCB1 (INI1) and SMARCA4 (BRG1). The Bush lab was one of the first groups to explore the use of BRG1 IHC to identify a subset of RTs that were INI1-retained. Further work is ongoing looking at the immune microenvironment of RTs as these are generally considered to have low tumor mutational burden and thus are immune-cold tumors, yet there appears to be heterogenous areas of tumor cell infiltration. Utilizing spatial genomics and proteomics, we hope to better understand RT inter and intra-tumoral heterogeneity.
Pediatric Bone Tumors The Bush lab uses fresh and fixed tumor tissue from the two most common malignant bone tumors, Osteosarcoma (OS) and Ewing Sarcoma (ES), to explore novel antibodies using immunohistochemistry (IHC) for diagnosis and prognosis. This includes developing tissue microarrays (TMAs) to test a number of antibodies across a wide variety of samples. Some work has shown that a particular methylation pattern in the diagnostic biopsies of OS may predict good or bad disease behaviour.
Novel Diagnostic and Precision Methods in Pediatric Tumors Working with collaborators, the Bush lab is helping to establish a proteomics pipeline that will demonstrate the utility of proteomics in clinical applications. This includes providing diagnostic, prognostic, and in some cases predictive markers that will allow for personalized therapies based on relative over or under-abundance of particular proteins. Promising results have been seen in OS and neuroblastoma to date. In collaboration with researchers at UBC and the NIH, the Bush lab is exploring the use of machine learning (ML) in osteosarcoma. This work will develop a pipeline for assessing tissue quality for the purpose of molecular studies, facilitate histologic classification of OS for clinical trials, and to explore potential prognostic markers as identified by supervised and unsupervised ML. The Bush lab has worked with collaborators in establishing a novel method of developing patient-derived xenografts using a less expensive model than the typical mouse system. Through this chorioallantoic membrane (CAM) modelling system, we have been able to facilitate tumor expansion in both highly aggressive and indolent tumors, and have worked to demonstrate the utility of the CAM system for drug testing.
Eosinophilic Esophagitis (EoE) Our group was the first to show that pediatric EoE was associated with increased lamina propria IgG4-positive plasma cells, which is being explored as to whether food-specific IgG4 can be used to evaluate for EoE disease activity. Ongoing work by the Bush lab has included utilizing novel techniques to evaluate EoE slides as well as potential spatial differences between the immune and squamous cell compartments.
Research Group Members
Daniela Buitrago, Graduate Research Assistant Michelle Dittrick, Clinical Research Program Manager
A pan-Canadian team has developed a new way to quickly find personalized treatments for young cancer patients, by growing their tumours in chicken eggs and analyzing their proteins.
The team, led by researchers from BC Children’s Hospital Research Institute and the University of British Columbia, is the first in Canada to combine these two techniques to identify and test a drug for a young patient's tumour in time for their treatment.
Congratulations to the investigators and their teams who were awarded funding through the Canadian Institutes of Health Research (CIHR) Fall 2024 Project Grant competition!
The findings from a BCCHR study played a part in integrating the multiple breath washout test into recent recommendations to screen children for pulmonary chronic graft-versus-host disease, a lung complication that can affect children who undergo a bone marrow transplant.
New research published in Nature Communications, identifies a key molecule that might be critical for the development of stem cell-based therapies for treating type 1 diabetes.
Dr. Kirk Schultz, an investigator at BC Children’s Hospital Research Institute, has been awarded the 2024 Geoffrey L. Hammond Lectureship in recognition of his leadership and significant contributions to improving the health and well-being of children in British Columbia and around the world.
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